1-Hydroxybenzotriazole → 2(R)-Hydroxy-3-[4-({indan-5-yl-[4-(4-trifluoromethoxyphenyl)thiazol-2-yl]amino}methyl)-benzoylamino]propionic acid methyl ester

HRID 1816175Notes

Reaction equation

HRID 1816175 reaction equation
[CH2:1]1[C:9]2[C:4](=[CH:5][C:6]([N:10]([CH2:27][C:28]3[CH:36]=[CH:35][C:31]([C:32](O)=[O:33])=[CH:30][CH:29]=3)[C:11]3[S:12][CH:13]=[C:14]([C:16]4[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[CH:18][CH:17]=4)[N:15]=3)=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.[CH3:60][O:61][C:62](=[O:67])[C@H:63]([OH:66])[CH2:64][NH2:65].CCN(C(C)C)C(C)C>CN(C=O)C.C(OCC)(=O)C>[CH3:60][O:61][C:62](=[O:67])[C@H:63]([OH:66])[CH2:64][NH:65][C:32](=[O:33])[C:31]1[CH:35]=[CH:36][C:28]([CH2:27][N:10]([C:6]2[CH:5]=[C:4]3[C:9](=[CH:8][CH:7]=2)[CH2:1][CH2:2][CH2:3]3)[C:11]2[S:12][CH:13]=[C:14]([C:16]3[CH:17]=[CH:18][C:19]([O:22][C:23]([F:25])([F:26])[F:24])=[CH:20][CH:21]=3)[N:15]=2)=[CH:29][CH:30]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 224963904-({Indan-5-yl-[4-(4-trifluoromethoxyphenyl)thiazol-2-yl]amino}methyl)benzoic acidHCID 86590828(R)-methyl 3-amino-2-hydroxypropanoate hydrochloride

Product 1

HCID 426376622(R)-Hydroxy-3-[4-({indan-5-yl-[4-(4-trifluoromethoxyphenyl)thiazol-2-yl]amino}methyl)-benzoylamino]propionic acid methyl ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-({Indan-5-yl-[4-(4-trifluoromethoxyphenyl)thiazol-2-yl]amino}methyl)benzoic acid (0.44 g, 0.86 mmol) was dissolved in DMF (10 mL) and 1-hydroxybenzotriazole (0.18 g, 1.29 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.25 g, 1.29 mmol) were added and the resulting mixture was stirred at room temperature for 1.5 hours. 3-Amino-2(R)-hydroxypropionic acid methyl ester hydrochloride, (R-isoserine methyl ester hydrochloride), prepared as described in WO 02/00612, (0.16 g, 1.03 mmol) and DIPEA (225 μL, 1.29 mmol) were added and the resulting mixture was stirred at room temperature for 16 hours. Ethyl acetate (100 mL) was added and the mixture was washed with water (2×80 mL). The organic phase was dried (MgSO4) and concentrated in vacuo. The residue (0.35 g) was purified by column chromatography on silica gel eluting with a mixture of ethyl acetate and heptane (1:1). This afforded 0.10 g (19%) of 2(R)-Hydroxy-3-[4-({indan-5-yl-[4-(4-trifluoromethoxyphenyl)thiazol-2-yl]amino}methyl)benzoylamino]propionic acid methyl ester.

Workup

  1. additionwere added
  2. stirringthe resulting mixture was stirred at room temperature for 16 hours
  3. washthe mixture was washed with water (2×80 mL)
  4. dry with materialThe organic phase was dried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue (0.35 g) was purified by column chromatography on silica gel eluting with a mixture of ethyl acetate and heptane (1:1)

Sources & evidence

ORD record
ord-85a8956d74db4243ac7b7039eee4f553
Source dataset
uspto-grants-2005_04
Patent number
US06881746B2

Reaction notes

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